This Midcareer Investigator Award application seeks support to provide Dr. Freedland with protected time for patient-oriented research (POR) and to act as research mentor for junior faculty and 1 research fellow per year. Dr. Freedland's POR focuses on retrospective cohort studies with a transitioning emphasis on prospective clinical trials aimed at developing new and less toxic treatments to minimize prostate cancer treatment side effects and slow prostate cancer progression. Herein, he proposes a new trial comparing a carbohydrate-restricted diet vs. control for men with PSA recurrence after prostate cancer therapy aiming to slow the rate of PSA rise (lengthen the PSA doubling time), as an indirect measure of slowed prostate cancer growth. Secondary outcomes include weight loss and important prostate cancer biomarkers. Successful completion of this award will advance our understanding of lifestyle and other low toxicity interventions for prostate cancer as well as help educate the next generation of POR investigators. PUBLIC HEALTH RELEVANCE: Prostate Cancer is a major public health burden. Despite great efforts, and some progress, today, prostate cancer remains the number two cancer killer of men and a significant source of morbidity. New and less toxic treatments aimed at both minimizing treatment side-effects and slowing disease progression at sorely needed. Moreover, a new generation of investigators focused on patient-oriented research (POR) is also needed. To these ends, this Midcareer Investigator Award application seeks support to provide Dr. Freedland with protected time for POR and to act as research mentor for junior faculty and 1 research fellow per year. While Dr. Freedland's POR focus to date has been largely on retrospective cohort studies, this award coincides with a shift in his POR toward prospective clinical trials aimed at developing new and less toxic treatments to minimize prostate cancer treatment side effects and slow prostate cancer progression. Moreover, Dr. Freedland is a proven successful mentor to junior investigators in training and this award allows him to continue to spend the time necessary to mentor and help train the next generation of POR investigators.